Various tumor related diseases inflict man. Considerable research has been devoted to oncology and antitumor measures. Tumors are common in a variety of mammals and the prevention, control of the growth and regression of tumors in mammals is important to man. The term tumor refers to abnormal masses of new tissue growth which is discordant with the economy of the tissue of orgin or of the host's body as a whole.
Tumors inflict mammals and man with a variety of disorders and conditions including various forms of cancer and resultant cancerous cachexia. Cancerous cachexia refers to the symptomatic discomfort that accompanies the infliction of a mammal with a tumor. These symptoms include weakened condition of the inflicted mammal as evidenced by, for example, weight loss. The seriousness of cancer is well known, e.g., cancer is second only to heart and vascular diseases as a cause of death in man.
Considerable research and resources have been devoted to oncology and antitumor measures including chemotherapy. While certain methods and chemical compositions have been developed which aid in inhibiting, remitting or controlling the growth of tumors new methods and antitumor chemical compositions are needed.
Marine organisms and particularly marine sponges are a potential source for chemically and biologically interesting molecules of great diversity. Some such molecules derived from sponges are described in Scheuer, P. J. Ed., Marine Natural Products, Chemical and Biological Perspectives; Academic Press; N.Y., 1978-1983; Vol. I-V; Faulkner, D. J. Natural Products Reports 1984, 551-598; Uemura, D.; Takahashi, K.; Yamamoto, T.; Katayama, C.; Tanaka, J.; Okumura, Y.; Hirata, Y. J. Am. Chem. Soc. 1985, 107, 4796-4798. The entire disclosures of these references are hereby incorporated herein by reference.
Other interesting compositions derived from marine organisms (i.e., caribbean tunicate) and containing a .beta.-Carboline system are described by K. L. Rinehart, Jr., J. Kobayashi, G. C. Harbour, R. G. Hughes, Jr., S. A. Mizsak, T. A. Scahill, in J. Am. Chem. Soc., 106, 1524 (1984); J. Kobayashi, G. C. Harbour, J. Gilmore and K. L. Rinehart, Jr., ibid., at 1526. Also of interest are compositions disclosed by R. Sakai, T. Higa, C. W. Jefford, and G. Bernardinelli, in J. Am. Chem. Soc., 108, 6404 (1986) and by H. Nakamura, S. Deng, J. Kobayaski, Y. Ohizumi, Y. Tomotake, T. Matsuzaki, and Y. Hirata, in Tetrahedron Lett., 28, 621 (1987).
Certain cyclic alkaloid compositions, e.g., manzamines A-D derived from extracts of the marine sponge Haliclona sp., have been found to possess useful antitumor activity. Co-pending applications of Higa et al., U.S. Ser. No. 879,094 filed June 26, 1986 and U.S. Ser. No. 943,609 filed Dec. 18, 1986 are directed to antitumor alkaloid compositions including manzamines A-D: ##STR1## the entire disclosures of these co-pending applications are hereby incorporated herein by reference. The present invention is also directed to useful antitumor alkaloid compositions which are derived from the marine sponge Xestospongia sp.